International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationPhase I Trial of Pelvic Nodal Dose Escalation With Hypofractionated IMRT for High-Risk Prostate Cancer
Introduction
The clinical benefit of pelvic nodal irradiation for prostate cancer has been difficult to establish and is uncertain. Although progression-free survival benefit has been reported in Radiation Therapy Oncology Group (RTOG) 94-13 at 5-year follow-up (1), updates of this study (2) and of other trials 3, 4 have either shown only trends or failed to demonstrate benefit using doses of 45–50.4 Gy. Salvage radiation data indicate improved biochemical control with increasing doses to the 66- to 70-Gy range when targeting microscopic disease in the prostatic fossa 5, 6, but prescribed pelvic nodal doses have been limited by toxicity concerns. Beyond well-known difficulties in reliably selecting patients at high risk for nodal involvement, one hypothesis for such uncertain benefit from pelvic radiotherapy is that contemporary doses from 45 to 50.4 Gy are suboptimal for controlling microscopic disease.
Advances and techniques such as intensity modulated radiation therapy (IMRT), bowel displacement techniques (7), and bladder filling can better facilitate limiting the dose to the small bowel while treating pelvic nodal basins. When using conventional fractionation for the pelvic nodes and the prostate, two separate three-dimensional conformal or IMRT plans must be generated; however, one IMRT plan may direct the entire treatment if hypofractionated radiotherapy is delivered to the prostate gland via a simultaneous integrated boost. Early evidence also suggests that hypofractionated radiotherapy may confer some additional advantage by increasing the therapeutic ratio because of a hypothesized low α/β ratio for prostate cancer (8).
We therefore tested whether image-guided IMRT can safely deliver escalated nodal doses while treating the prostate simultaneously with a hypofractionated schedule. We present a dose–volume analysis of toxicities and preliminary biochemical control estimates in 53 high pelvic nodal risk patients treated to a nodal dose of 56 Gy in 2-Gy fractions with concomitant treatment of the prostate to 70 Gy in 2.5-Gy fractions, with the entire treatment delivered in 28 fractions.
Section snippets
Methods and Materials
Patients with high-risk prostate adenocarcinoma with prediction of ≥10% pelvic lymph node involvement (9) were eligible for treatment on this Phase I prospective protocol, approved by the institutional review board of the University of Wisconsin Hospital. In addition, any patient with radiographic evidence of pelvic lymph node involvement but absence of distal metastases could be enrolled in the protocol. No patient had evidence of distal metastases on bone scan and computed tomography (CT) of
Results
Between August 2004 and September 2008, a total of 53 patients were treated. Fifty patients received ADT for a median duration of 12 months (range 3–28 months), with 3 patients not so treated because of patient refusal. Patient characteristics are detailed in Table 1. The dosimetric parameters achieved using IMRT to spare organs at risk are detailed in Table 2. The median follow-up time was 25.4 months (range, 4.2–57.2 months).
Discussion
Pelvic nodal irradiation, delivered with various schedules of ADT, has been the historic standard for locally advanced prostate cancer 13, 14, 15, 16. The two minimum requirements for clinical benefit from pelvic radiotherapy are the selection of patients at sufficiently high risk for nodal metastatic involvement and the safe delivery of radiation doses sufficiently high to sterilize nodal metastases.
Several models have estimated the risk of pelvic nodal involvement 17, 18, 19, 20, 21, many of
Conclusion
Pelvic nodal IMRT dose escalation to 56 Gy delivered concurrently with 70 Gy of hypofractionated prostate radiotherapy in 28 fractions over 5½ weeks is a resource- efficient, convenient, and well-tolerated regimen that produces acceptable preliminary biochemical control rates. No in-field pelvic nodal failures have been observed to date despite two periaortic failures outside the treatment volume. Although the benefits of pelvic nodal irradiation using conventional 45- to 50.4-Gy doses remain
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Long-Term Results of Moderate Hypofractionation to Prostate and Pelvic Nodes Plus Androgen Suppression in High-Risk Prostate Cancer
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Supported by NCI Grant R01CA106835.
Conflict of interest: none.